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AR056197A1 - DERIVATIVES OF 7-METHYLIMIDAZOL [1,2-A] PIRIDIN-6-IL-8-METHYL-NONAMIDS AS INHIBITORS OF THE RENIN, PHARMACEUTICAL COMPOSTIONS CONTAINING THEM AND THEIR USE IN THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF ARTERIAL HYPERTENSION - Google Patents

DERIVATIVES OF 7-METHYLIMIDAZOL [1,2-A] PIRIDIN-6-IL-8-METHYL-NONAMIDS AS INHIBITORS OF THE RENIN, PHARMACEUTICAL COMPOSTIONS CONTAINING THEM AND THEIR USE IN THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF ARTERIAL HYPERTENSION

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Publication number
AR056197A1
AR056197A1 ARP060104027A ARP060104027A AR056197A1 AR 056197 A1 AR056197 A1 AR 056197A1 AR P060104027 A ARP060104027 A AR P060104027A AR P060104027 A ARP060104027 A AR P060104027A AR 056197 A1 AR056197 A1 AR 056197A1
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Argentina
Prior art keywords
alkyl
alkoxy
amino
aminocarbonyl
carbamoyl
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ARP060104027A
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Spanish (es)
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Speedel Experimenta Ag
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Publication of AR056197A1 publication Critical patent/AR056197A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Estos compuestos, tienen propiedades inhibidoras de la renina y se pueden usar como medicinas en composiciones farmacéuticas para el tratamiento de la hipertension. Reivindicacion 1: Un compuesto de la formula (1), en donde X es -CH2- o >CH-OH; (A) R1 es cuando X es hidroximetileno, ya sea un radical heterociclilo opcionalmente substituido o un radical hidrocarbonado intsaturado policíclico opcionalmente substituido, o (B) R1 es un radical heterociclilo mono- a tetrasubstituido, o un radical hidrocarbonado insaturado policíclico opcionalmente mono- a tetrasubstituido, donde los substituyentes de dichos radicales están seleccionados de modo independiente entre sí, del grupo que consiste en acetamidinil-alquilo C1-6, 3- acetamidometilpirrolidinilo, acil-alcoxi C1-6-alquilo C1-6, (N-acil)-alcoxi C1-6-alquil C1-6-amino, alcanoilo C1-6, alcanoil C1-6-oxi, alquenilo C2-6, alquenil C1-6-oxi, alquenil C1-6-oxi-alquilo C1-6, alcoxi C1-6, alcoxi C1-6-alcoxi C1-6, alcoxi C1- 6-alcoxi C1-6-alquilo C1-6, alcoxi C1-6-alquilo C1-6, (N-alcoxi C1-6)-alquil C1-6-aminocarbonil-alcoxi C1-6, (N-alcoxi C1-6)-alquil C1-6-aminocarbonil-alquilo C1-6, alcoxi C1-6-alquil C1-6-carbamoilo, alcoxi C1-6-alquil C1-6-carbonilo, alcoxi C1-6- alquil C1-6-carbonilamino, 1-alcoxi C1-6-alquil C1-6-imidazol-2-ilo, 2-alcoxi C1-6-alquil C1-6-4-oxoimidazol-1-ilo, 3-alcoxi C1-6-alquil C1-6-pirrolidinilo, 1-alcoxi C1-6-alquil C1-6-tetrazol-5-ilo, 5-alcoxi C1-6-alquil C1-6-tetrazol-1-ilo, alcoxi C1-6-aminocarbonil-alcoxi C1-6, alcoxi C1-6-aminocarbonil-alquilo C1-6, alcoxi C1-6-carbonilo, alcoxi C1-6-carbonil-alcoxi C1-6, alcoxi C1-6-carbonil-alquilo C1-6, alcoxi C1-6-carbonilamino, alcoxi C1-6-carbonilamino-alcoxi C1-6, alcoxi C1-6- carbonilamino-alquilo C1-6, alquilo C1-6, (N-alquil C1-6)-alcoxi C1-6-alquil C1-6-carbamoilo, (N-alquil C1-6)-alcoxi C1-6-alquil C1-6-carbonilamino, (N-alquil C1-6)-alcoxi C1-6-carbonilamino, (N-alquil C1-6)-alquil C0-6-carbonilamino-alcoxi C1-6, (N- alquil C1-6)-alquil C0-6-carbonilamino-alquilo C1-6, (N-alquil C1-6)-alquil C1-6-sulfonilamino-alcoxi C1-6, (N-alquil C1-6)-alquil C1-6-sulfonilamino-alquilo C1-6, alquil C1-6-amidinilo, alquil C1-6-amino, di-alquil C1-6-amino, alquil C1-6-amino- alcoxi C2-6, di-alquil C1-6-amino-alcoxi C2-6, alquil C1-6-amino-alquilo C1-6, alquil C1-6-aminocarbonilo, alquil C1-6-aminocarbonil-alcoxi C1-6, di-alquil C1-6-aminocarbonil-alcoxi C1-6, alquil C1-6-aminocarbonil-alcoxi C1-6-alquilo C1-6, alquil C1- 6-aminocarbonil-alquilo C1-6, alquil C1-6-aminocarbonilamino-alcoxi C1-6, alquil C1-6-aminocarbonilamino-alquilo C1-6, di-alquil C1-6-aminocarbonil-alquilo C1-6, di-alquil C1-6-amino-alquilo C1-6, alquil C1-6-carbamoilo, di-alquil C1-6-carbamoilo, alquil C0-6-carbonilamino, alquil C0-6-carbonilamino-alcoxi C1-6, alquil C0-6-carbonilamino C0-6-alquilo C1-6, alquil C1-6-carboniloxi-alcoxi C1-6, alquil C1-6-carboniloxi-alquilo C1-6, alquilen C1-6-dioxi, alquil C1-6-sulfonilo, alquil C1-6- sulfonil-alcoxi C1-6, alquil C1-6-sulfonil-alquilo C1-6, alquil C1-6-sulfonilamino-alcoxi C1-6, alquil C1-6-sulfonilamino-alquilo C1-6, amino, amino-alcoxi C2-7, amino-alquilo C1-6, aril-alcanoilo C1-6, benzoiloxi-alcoxi C2-6, carbamoilo, carbamoil- alcoxi C1-6, carbamoil-alquilo C1-6, carboxi, carboxi-alcoxi C1-6, carboxi-alcoxi C1-6-alquilo C1-6, carboxi-alquilo C1-6, ciano, ciano-alcoxi C1-6, ciano-alquilo C1-6, cicloalquil C3-8-alcanoilo C1-6, cicloalquil C3-8-alcoxi C0-6, cicloalquil C3-8- alquilo C0-6, cicloalquil C3-8-carbonilamino, cicloalquil C3-8-carbonilamino-alcoxi C1-6, cicloalquil C3-8-carbonilamino-alquilo C1-6, 3,4-dihidroxipirrolidinilo, O,N-dimetilhidroxilamino-alquilo C1-6, 2,6-dimetilmorfolinilo, 3,5-dimetilmorfolinilo, dioxanilo, dioxolanilo, dioxolanil-alcoxi C1-6, 4,4-dioxotiomorfolinilo, ditianilo, ditiolanilo, furilo opcionalmente substituido con alcoxi C1-6, alquilo C1-6, dihidroxi-alquil C1-6-aminocarbonilo o halogeno, furil-alcoxi C1-6, furil-alquilo C1-6, piridilo, piridil-alcoxi C1-6, piridil-alquilo C1-6, piridil-amino, piridiloxi, piridiltio, pirimidinilo, pirimidinil-alcoxi C1-6, pirimidinil-alquilo C1-6, pirimidinilamino, pirimidiniloxi, pirimidiniltio, tienilo, tienil-alcoxi C1-6 o tienil- alquilo C1-6, halogeno, heterociclil-alcanoilo C1-6, hidroxi, hidroxi-alcoxi C2-6, hidroxi-alcoxi C2-6-alcoxi C1-6, hidroxi-alcoxi C2-6-alquilo C1-6, hidroxi-alquilo C1-6, (N-hidroxi)-alquil C1-6-aminocarbonil-alcoxi C1-6, (N-hidroxi)-alquil C1-6- aminocarbonil-alquilo C1-6, (N-hidroxi)aminocarbonil-alcoxi C1-6, (N-hidroxi)aminocarbonil-alquilo C1-6, hidroxi-benciloxi, 2-hidroximetilpirrolidinilo, 4-hidroxipiperidinilo, 3-hidroxipirrolidinilo, imidazolil-alcoxi C1-6, imidazolil-alquilo C1-6, metoxibenciloxi, metilendioxibencil-oxi, 2-metilimidazolil-alcoxi C1-6, 2-metilimidazolil-alquilo C1-6, 3-metil-[1,2,4]-oxadiazol-5-il-alcoxi C1-6, 5-metil-[1,2,4]-oxadiazol-3-il-alcoxi C1-6, 3-metil-[1,2,4]-oxadiazol-5-il-alquilo C1-6, 5-metil- [1,2,4]-oxadiazol-3-il-alquilo C1-6, O-metil-oximil-alquilo C1-6, 4-metilpiperazinilo, N-metilpiperazino-alcoxi C1-6, N-metilpiperazino-alcoxi C1-6-alquilo C1-6, N-metilpiperazino-alquilo C1-6, 5-metiltetrazol-1-il-alcoxi C1-6, 5-metiltetrazol-1-il- alquilo C1-6, morfolinilo, morfolino-alcoxi C1-6, morfolino-alcoxi C1-6-alquilo C1-6, morfolino-alquilo C1-6, nitro, [1,2,4]-oxadiazol-5-il-alcoxi C1-6, [1,2,4]-oxadiazol-5-il-alquilo C1-6, oxazol-4-il-alcoxi C1-6, oxazol-4-il-alquilo C1-6, oxido, oxo, 2-oxoimidazolidinilo, 2-oxo-[1,3]oxazinilo, 2-oxooxazolidinilo, 2-oxooxazolidinil-alcoxi C1-6, 2-oxooxazolidinil-alquilo C1-6, 4-oxopiperidinilo, 2-oxopirrolidinilo, 2-oxo-pirrolidinil-alcoxi C1-6, 2-oxopirrolidinil-alquilo C1-6, 2- oxotetrahidropirimidinilo, 4-oxotiomorfolinilo, fenoxi opcionalmente substituido con alcoxi C1-6, alcoxi C1-6-carbonilo, alquilo C1-6, alquil C1-6-amino, di-alquil C1-6-amino, halogeno, hidroxilo, hidroxi-alquilo C1-6 o trifluorometilo, fenilo, fenil-alcoxi C1-6, fenil-alquilo C1-6 o feniltio, piperazinilo, piperazino-alcoxi C1-6, piperazino-alcoxi C1-6-alquilo C1-6, piperazino-alquilo C1-6, piperidinilo, piperidino-alcoxi C1-6, piperidino-alcoxi C1-6-alquilo C1-6, polihalogen-alcoxi C1-6, polihalogen-alquilo C1-6, piridilcarbamoiloxi-alcoxi C1-6, piridilcarbonilamino-alquilo C1-6, pirrolidinilo, pirrolilo, tetrazol-1-il-alcoxi C1-6, tetrazol-2-il-alcoxi C1-6, tetrazol-5-il-alcoxi C1-6, tetrazol-1-il-alquilo C1-6, tetrazol-2-il- alquilo C1-6, tetrazol-5-il-alquilo C1-6, tiazol-4-il-alcoxi C1-6, tiazol-4-il-alquilo C1-6, tiomorfolinilo, [1,2,4]-triazol-1-il-alcoxi C1-6, [1,2,4]-triazol-4-il-alcoxi C1-6, [1,2,4]-triazol-1-il-alquilo C1-6, [1,2,4]-triazol-4-il-alquilo C1-6 y el radical -O-CH2CH(OH)CH2NRx, donde NRx es un mono- o di-alquil C1-6-amino, N-metilpiperazino, morfolino, piperazino o piperidino, y donde (a) en el caso en que R1 sea naftilo o ciclohexenofenilo, al menos el anillo no unido directamente con X está substituido como se indico; (b) en el caso en que R1 sea un sistema de anillos heterocíclicos bicíclicos, al menos el anillo no unido directamente con X está substituido como se indico; R2 es alquilo C1-6 o cicloalquilo C3-6; R3 es, de modo independiente entre sí, H, alquilo C1-6, alcoxi C1-6-carbonilo o alcanoilo C1-6; R4 es alquenilo C2-6, alquilo C1-6, aril-alquilo C1-6 o cicloalquilo C3-8 no substituido o substituido; R5 es alcanoil C1-6-amido-alquilo C1-6, alcanoil C1-6-oxi- alquilo, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6-alquilo C1-6, alcoxi C1-6-carbonil-alquilo C1-6, alquilo C1-6, alquil C1-6-amino-alquilo C1-6, di-alquil C1-6-amino-alquilo C1-6, amino-alquilo C1-6, N-(alquil C1-6)-carbamoil-alquilo C1-6, di- alquil-carbamoil-alquilo C1-6, aril-alquilo C0-6 opcionalmente substituido, carbamoil-alquilo C1-6, carboxi-alquilo C1-6, ciano-alquilo C1-6, cicloalquil C3-8-alquilo C1-6, opcionalmente substituido, heterociclil-alquilo C0-6, hidroxi-alquilo C1-6 o polihalogen-alquilo C1-6; o su sal, profármaco o un compuesto en donde uno o varios átomos se reemplazan por sus isotopos estables no radiactivos, en particular su sal farmacéuticamente aceptable.These compounds have renin inhibitory properties and can be used as medicines in pharmaceutical compositions for the treatment of hypertension. Claim 1: A compound of the formula (1), wherein X is -CH2- or> CH-OH; (A) R1 is when X is hydroxymethylene, either an optionally substituted heterocyclyl radical or an optionally substituted polycyclic unsaturated hydrocarbon radical, or (B) R1 is a mono-to tetrasubstituted monocyclic heterocyclyl radical, or an optionally mono-a polycyclic unsaturated hydrocarbon radical tetrasubstituted, where the substituents of said radicals are independently selected from each other, from the group consisting of acetamidinyl-C 1-6 alkyl, 3- acetamidomethylpyrrolidinyl, acyl-C 1-6 alkoxy-C 1-6 alkyl, (N-acyl) - C 1-6 alkoxy-C 1-6 alkyl amino, C 1-6 alkanoyl, C 1-6 alkanoyl, C 2-6 alkenyl, C 1-6 alkenyl, C 1-6 alkenyl-C 1-6 alkyl, C 1-6 alkoxy -6, C 1-6 alkoxy-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, (N-C 1-6 alkoxy) -C 1-6 alkyl 6-aminocarbonyl-C 1-6 alkoxy, (N-C 1-6 alkoxy) -C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-carbamoyl, C 1-6 alkoxy-C 1-6 alkyl 6-carbonyl, C1-6 alkoxy- C1-6-c alkyl arbonylamino, 1-C 1-6 alkoxy-C 1-6 alkyl-imidazol-2-yl, 2-C 1-6 alkoxy-C 1-6 alkyl-oxoimidazol-1-yl, 3-C 1-6 alkoxy-C 1-6 alkyl 6-pyrrolidinyl, 1-C 1-6 alkoxy-C 1-6 alkyl-tetrazol-5-yl, 5-C 1-6 alkoxy-C 1-6 alkyl-tetrazol-1-yl, C 1-6 alkoxy-aminocarbonyl-C 1- alkoxy 6, C 1-6 alkoxycarbonyl-C 1-6 alkyl, C 1-6 alkoxycarbonyl, C 1-6 alkoxycarbonylC 1-6 alkoxy, C 1-6 alkoxycarbonylC 1-6 alkyl, C 1-6 alkoxy carbonylamino, C 1-6 alkoxycarbonylamino C 1-6 alkoxy, C 1-6 alkoxycarbonylamino C 1-6 alkyl, C 1-6 alkyl, (N-C 1-6 alkyl) -C 1-6 alkoxy-C 1-6 alkyl carbamoyl, (N-C1-6 alkyl) -C 1-6 alkoxy-C1-6 alkylcarbonylamino, (N-C1-6 alkyl) -C 1-6 alkoxycarbonylamino, (N-C1-6 alkyl) -C0 alkyl -6-carbonylamino-C1-6 alkoxy, (N- C1-6 alkyl) -C0-6 alkylcarbonylamino-C1-6 alkyl, (N-C1-6 alkyl) -C1-6 alkyl-sulfonylamino-C1-alkoxy 6, (N-C1-6 alkyl) -C 1-6 alkyl-sulfonylamino-C1-6 alkyl, C1-6-amidinyl alkyl, C1-6-amino alkyl, di-C1-6-amino alkyl, C1-6 alkyl -amino- C2-6 alkoxy, di-C-alkyl 1-6-C2-6 amino-alkoxy, C1-6-alkyl-C1-6-alkyl, C1-6-alkylcarbonyl, C1-6-alkylcarbonyl-C1-6-alkoxy, di-C1-6-alkylcarbonyl -C 1-6 alkoxy, C 1-6 alkyl-aminocarbonyl-C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl, C 1-6 alkyl-aminocarbonylamino-C 1-6 alkoxy, C 1-6 alkyl 6-aminocarbonylamino-C 1-6 alkyl, di-C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl, di-C 1-6 alkyl-amino-C 1-6 alkyl, C 1-6 alkyl-carbamoyl, di-C 1-6 alkyl -carbamoyl, C0-6 alkylcarbonylamino, C0-6 alkylcarbonylaminoC 1-6 alkoxy, C0-6 alkylcarbonylamino C0-6-C1-6 alkyl, C1-6 alkylcarbonyloxy-C1-6 alkoxy alkyl C1-6-carbonyloxy-C1-6 alkyl, C1-6-dioxy alkyl, C1-6-sulfonyl alkyl, C1-6-sulfonyl-C1-6 alkoxy, C1-6 alkyl-sulfonyl-C1-6 alkyl alkyl C1-6-sulfonylamino-C1-6 alkoxy, C1-6 alkyl-sulfonylamino-C1-6 alkyl, amino, aminoC2-7 alkoxy, amino- C1-6 alkyl, aryl-C1-6 alkanoyl, benzoyloxy-C2 alkoxy -6, carbamoyl, carbamoyl-C1-6 alkoxy, carbamoyl-C alkyl 1-6, carboxy, carboxy-C1-6 alkoxy, carboxy-C1-6 alkoxy-C1-6 alkyl, carboxy-C1-6 alkyl, cyano, cyano-C1-6 alkoxy, cyano-C1-6 alkyl, C3 cycloalkyl -8-C 1-6 alkanoyl, C 3-8 cycloalkyl-C 0-6 alkoxy, C 3-8 cycloalkyl, C 0-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-6 alkyloxy, C 3-6 cycloalkyl 8-carbonylamino-C 1-6 alkyl, 3,4-dihydroxypyrrolidinyl, O, N-dimethylhydroxylamino-C 1-6 alkyl, 2,6-dimethylmorpholinyl, 3,5-dimethylmorpholinyl, dioxanyl, dioxolanyl, dioxolanyl-C 1-6 alkoxy, 4 , 4-dioxothiomorpholinyl, dithianyl, dithiolanyl, furyl optionally substituted with C1-6 alkoxy, C1-6 alkyl, dihydroxy C1-6 alkylcarbonyl or halogen, furyl C1-6 alkoxy, furyl C1-6 alkyl, pyridyl, pyridyl-C 1-6 alkoxy, pyridyl-C 1-6 alkyl, pyridyl-amino, pyridyloxy, pyridylthio, pyrimidinyl, pyrimidinyl-C 1-6 alkoxy, pyrimidinyl-C 1-6 alkyl, pyrimidinylamino, pyrimidinyloxy, pyrimidinylthio, thienyl, thienyl-C 1 -alkoxy -6 or thienyl-C 1-6 alkyl, halogen, heterocyclyl-a C1-6 alkanoyl, hydroxy, C2-6 hydroxy-alkoxy, C2-6 alkoxy-C1-6 alkoxy, hydroxyC2-6 alkoxy-C1-6 alkyl, hydroxy-C1-6 alkyl, (N-hydroxy) -C 1-6 alkyl-aminocarbonyl-C 1-6 alkoxy, (N-hydroxy) -C 1-6 alkyl-aminocarbonyl-C 1-6 alkyl, (N-hydroxy) aminocarbonyl-C 1-6 alkoxy, (N-hydroxy) aminocarbonyl- C1-6 alkyl, hydroxybenzyloxy, 2-hydroxymethylpyrrolidinyl, 4-hydroxypiperidinyl, 3-hydroxypyrrolidinyl, imidazolyl-C1-6 alkoxy, imidazolyl-C1-6 alkyl, methoxybenzyloxy, methylenedioxybenzyl-oxy, 2-methylimidazolyl 2-methylimidazolyl-C1-6 alkyl, 3-methyl- [1,2,4] -oxadiazol-5-yl-C1-6 alkoxy, 5-methyl- [1,2,4] -oxyadiazol-3-yl- C1-6 alkoxy, 3-methyl- [1,2,4] -oxadiazol-5-yl-C1-6 alkyl, 5-methyl- [1,2,4] -oxadiazol-3-yl-C1-6 alkyl , O-methyl-oximyl-C1-6 alkyl, 4-methylpiperazinyl, N-methylpiperazino-C1-6 alkoxy, N-methylpiperazino-C1-6 alkoxy-C1-6 alkyl, N-methylpiperazino-C1-6 alkyl, 5- methyltetrazol-1-yl-C1-6 alkoxy, 5-methyltetrazol-1-yl-C1-6 alkyl, morpholinyl, morpholino-C alkoxy 1-6, morpholino-C 1-6 alkoxy-C 1-6 alkyl, morpholino-C 1-6 alkyl, nitro, [1,2,4] -oxadiazol-5-yl-C 1-6 alkoxy, [1,2,4 ] -oxadiazol-5-yl-C 1-6 alkyl, oxazol-4-yl-C 1-6 alkoxy, oxazol-4-yl-C 1-6 alkyl, oxido, oxo, 2-oxoimidazolidinyl, 2-oxo- [1, 3] oxazinyl, 2-oxooxazolidinyl, 2-oxooxazolidinyl-C1-6 alkoxy, 2-oxooxazolidinyl-C1-6 alkyl, 4-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxo-pyrrolidinyl-C1-6 alkoxy, 2-oxopyrrolidinyl-alkyl C1-6, 2- oxotetrahydropyrimidinyl, 4-oxothiomorpholinyl, phenoxy optionally substituted with C1-6 alkoxy, C1-6 alkoxycarbonyl, C1-6 alkyl, C1-6-alkyl, di-C1-6-alkyl, halogen , hydroxy, hydroxy-C 1-6 alkyl or trifluoromethyl, phenyl, phenyl-C 1-6 alkoxy, phenyl-C 1-6 alkyl or phenylthio, piperazinyl, piperazino-C 1-6 alkoxy, piperazino-C 1-6 alkoxy-C 1-6 alkyl , piperazino-C 1-6 alkyl, piperidinyl, piperidino-C 1-6 alkoxy, piperidino-C 1-6 alkoxy-C 1-6 alkyl, polyhalogen-C 1-6 alkoxy, polyhalogen-C 1-6 alkyl, pyridylcarbamoyloxy-C 1-6 alkoxy, pirid ilcarbonylamino-C 1-6 alkyl, pyrrolidinyl, pyrrolyl, tetrazol-1-yl-C 1-6 alkoxy, tetrazol-2-yl-C 1-6 alkoxy, tetrazol-5-yl-C 1-6 alkoxy, tetrazol-1-yl C1-6 alkyl, tetrazol-2-yl-C1-6 alkyl, tetrazol-5-yl-C1-6 alkyl, thiazol-4-yl-C1-6 alkoxy, thiazol-4-yl-C1-6 alkyl, thiomorpholinyl , [1,2,4] -triazol-1-yl-C1-6 alkoxy, [1,2,4] -triazol-4-yl-C1-6 alkoxy, [1,2,4] -triazol-1 -yl-C1-6 alkyl, [1,2,4] -triazol-4-yl-C1-6 alkyl and the radical -O-CH2CH (OH) CH2NRx, where NRx is a mono- or di-C1-alkyl 6-amino, N-methylpiperazino, morpholino, piperazino or piperidino, and where (a) in the case where R1 is naphthyl or cyclohexenophenyl, at least the ring not directly linked with X is substituted as indicated; (b) in the case where R1 is a bicyclic heterocyclic ring system, at least the ring not directly linked with X is substituted as indicated; R2 is C1-6 alkyl or C3-6 cycloalkyl; R3 is, independently of each other, H, C1-6 alkyl, C1-6 alkoxycarbonyl or C1-6 alkanoyl; R4 is C2-6 alkenyl, C1-6 alkyl, aryl-C1-6 alkyl or unsubstituted or substituted C3-8 cycloalkyl; R5 is C1-6 alkanoyl-amido-C1-6 alkyl, C1-6 alkanoyl-oxy alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy-C1-6 alkyl, C1-6 alkoxycarbonyl- C1-6 alkyl, C1-6 alkyl, C1-6 alkyl-C1-6 alkyl, di-C1-6 alkyl-C1-6 alkyl, amino C1-6 alkyl, N- (C1-6 alkyl ) -carbamoyl-C 1-6 alkyl, di-alkyl-carbamoyl-C 1-6 alkyl, optionally substituted C 1-6 aryl-alkyl, carbamoyl-C 1-6 alkyl, carboxy-C 1-6 alkyl, cyano-C 1-6 alkyl, C3-8 cycloalkyl-C1-6 alkyl, optionally substituted, heterocyclyl-C0-6 alkyl, hydroxy-C1-6 alkyl or polyhalogen-C1-6 alkyl; or its salt, prodrug or a compound wherein one or more atoms are replaced by their stable non-radioactive isotopes, in particular their pharmaceutically acceptable salt.

ARP060104027A 2005-09-17 2006-09-14 DERIVATIVES OF 7-METHYLIMIDAZOL [1,2-A] PIRIDIN-6-IL-8-METHYL-NONAMIDS AS INHIBITORS OF THE RENIN, PHARMACEUTICAL COMPOSTIONS CONTAINING THEM AND THEIR USE IN THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF ARTERIAL HYPERTENSION AR056197A1 (en)

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